Retroviruses contain RNA as their genomic material. RNA may be transcribed to double-standard DNA form via an enzyme known as reverse transcriptase. When the viral DNA is incorporated into the genomic DNA of a host cell, it is called a provirus (also known as an endogenous retrovirus). As a consequence, the viral gene is replicated along with the cell chromosome and is thus expressed not only in the original, but in all of its progeny. A complete provirus consists of three distinct genes (gag, pol, env) as well as regulatory elements known as long terminal repeates (LTR) at both ends of the provirus. The gag gene codes for structural proteins of the virus, the pol gene codes for the reverse transcriptase enzyme and the env gene codes for envelope glycoproteins. All these genes are transcribed when a complete infectious endogenous retrovirus is produced. However, in many instances, only part of proviral DNA is transcribed and translated, i.e., only gag and pol genes, thus producing an incomplete virus.
Endogenous retroviruses are ubiquitous in animals. They have been recovered from several primates. A major source for isolation of endogenous retrovirus from baboons is the placenta. Particles resembling type C or type D retroviruses have also been seen budding from the syncytiotrophoblast layer of human placentas and from cultured teratocarcinoma cells. In addition, small retrovirus-like particles have been seen in human oocytes. Human endogenous retroviruses have not been isolated in an infectious form and producer cell lines have not been established.
Evidence has been presented that human DNA contains retrovirus-related nucleotide sequences. Nucleic acid reassociation studies first revealed that humans and other primates contain multiple baboon endogenous virsu (BaEV) related sequences in their chromosomal DNA. See, for example, Benveniste, R. E. & Todaro, G. J., Proc. Natl. Acad. Sci. USA, Vol. 71, pp. 4513-4518 (1974). A defective, endogenous provirus was isolated from a human recombinant DNA library by using an endogenous chimpanzee retroviral pol fragment as probe. The structure of this fragment is highly related to that of BaEV. This genome, termed HC-20 (or endogenous retrovirus-1; erv-1), has been assigned to human chromosome 18. See O'Brien, S. J., Bonner, T. I., et al., Nature (London), Vol. 303, pp. 74-77 (1983). The erv-1 provirus contains gag and pol genes, which are significantly related to those of both Moloney murine leukemia virus (Mo-MuLV) and BaEV, env related sequences of the expected length, and a 3' long terminal repeat (LTR), but no 5' LTR.
It is known that human placental syncytiotrophoblasts contain an antigen which is detected by a specific polyclonal antibody against the major structural protein p30 of the feline endogenous retrovirus RD114 which is highly related to BaEV. See, Suni, J., Wahlstrom, T., & Vaheri, A., Int. J. Cancer, Vol. 28, pp. 559-566 (1981). A study of 1540 human cord blood sera revealed the presence of RD114 p30 reactive antibodies in 118 (7.7%) sera. Antibodies to synthetic peptides, which were based on MuLV p30 amino acid sequences or sequences of env genes, have been found to be reactive with the native structural proteins of murine retroviruses.
The presence of these antibodies in the cord blood sera is highly correlated (p&lt;0.00005) to complications during pregnancy and to the number of previous abortions. The antigen, reactive with the antibodies to RD114 p30, is also detected in the tumor cells of renal calls adenocarcinoma, also known as hypernephroma. In immunohistochemical staining this antigenic material can be seen also in the lumen of proximal tubuli of the kidneys as a sign of its excretion to urine. Using a radioimmunoassay, with RD114 virus p30 protein and its specific antibody as reagents, antigenic material can be shown to be excreted into the urine of renal cell adenocarcinoma patients but not of normal individuals.
In 1975, Kohler and Milstein develoed a method of establishing a continuous hybrid cell line (hybridoma) derived by the fusion of murine myeloma cells to spleen cells from an immunized mouse which secreted a monoclonal antibody which binds to only one antigenic site; Nature, Vol. 256, p. 495 (1975). This method has subsequently been used by those familiar with the art to derive different kinds of monoclonal antibodies, See, for example, Melchers, F., Potter, M., et al., "Lymphocyte Hybridomas", Current Topics in Microbiology and Immunology, Vol. 81 (1978). Some compounds may not be immunogenic unless coupled to a carrier which is itself immunogenic; see, for example, Eisen, H. N., Immunology, Harper & Row (1980). Such compounds are called haptens and there are many methods known for attaching them to carriers in order to render the hapten immunogenic.
These methods may be used to create monoclonal or polyclonal antibodies to an undecapeptide, which has partial sequence homology to MuLV and BaEV-p30 proteins. The undecapeptide sequence was inferred from the nucleotide sequence of the human proviral locus, erv-1. These antibodies detect a polypeptide antigen in syncytiotrophoblastic cells of human placentas both in vivo and in culture.